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| | <StructureSection load='5xgp' size='340' side='right'caption='[[5xgp]], [[Resolution|resolution]] 2.08Å' scene=''> | | <StructureSection load='5xgp' size='340' side='right'caption='[[5xgp]], [[Resolution|resolution]] 2.08Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xgp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XGP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XGP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xgp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XGP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.077Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">szl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xgp OCA], [http://pdbe.org/5xgp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xgp RCSB], [http://www.ebi.ac.uk/pdbsum/5xgp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xgp ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5xgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xgp OCA], [https://pdbe.org/5xgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xgp RCSB], [https://www.ebi.ac.uk/pdbsum/5xgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xgp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O73821_XENLA O73821_XENLA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: African clawed frog]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Li, Z]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Liu, H]] | + | [[Category: Li Z]] |
| - | [[Category: Xu, F]] | + | [[Category: Liu H]] |
| - | [[Category: Secreted protein]] | + | [[Category: Xu F]] |
| - | [[Category: Unknown function]]
| + | |
| Structural highlights
Function
O73821_XENLA
Publication Abstract from PubMed
The Wnt-signaling pathway is crucial to cell proliferation, differentiation, and migration. The secreted Frizzled-related proteins (sFRPs) represent the largest family of secreted Wnt inhibitors. However, their function in antagonizing Wnt signaling has remained somewhat controversial. Here, we report the crystal structure of Sizzled from Xenopus laevis, the first full-length structure of an sFRP. Tethered by an inter-domain disulfide bond and a linker, the N-terminal cysteine-rich domain (CRD) and the C-terminal netrin-like domain (NTR) of Sizzled are arranged in a tandem fashion, with the NTR domain occluding the groove of CRD for Wnt accessibility. A Dual-Luciferase assay demonstrated that removing the NTR domain and replacing the CRD groove residues His-116 and His-118 with aromatic residues may significantly enhance antagonistic function of Sizzled in inhibiting Wnt3A signaling. Sizzled is a monomer in solution, and Sizzled CRD exhibited different packing in the crystal, suggesting that sFRPs do not have a conserved CRD dimerization mode. Distinct from the canonical NTR domain, the Sizzled NTR adopts a novel alpha/beta folding with two perpendicular helices facing the central mixed beta-sheet. The subgroup of human sFRP1/2/5 and Sizzled should have a similar NTR domain that features a highly positively charged region, opposite the NTR-CRD interface, suggesting that the NTR domain in human sFRPs, at least sFRP1/2/5, is unlikely to bind to Wnt but is likely involved in biphasic Wnt signaling modulation. In summary, the Sizzled structure provides the first insights into how the CRD and the NTR domains relate to each other for modulating Wnt-antagonistic function of sFRPs.
The crystal structure of full-length Sizzled from Xenopus laevis yields insights into Wnt-antagonistic function of secreted Frizzled-related proteins.,Bu Q, Li Z, Zhang J, Xu F, Liu J, Liu H J Biol Chem. 2017 Sep 29;292(39):16055-16069. doi: 10.1074/jbc.M117.791756. Epub , 2017 Aug 14. PMID:28808056[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bu Q, Li Z, Zhang J, Xu F, Liu J, Liu H. The crystal structure of full-length Sizzled from Xenopus laevis yields insights into Wnt-antagonistic function of secreted Frizzled-related proteins. J Biol Chem. 2017 Sep 29;292(39):16055-16069. doi: 10.1074/jbc.M117.791756. Epub , 2017 Aug 14. PMID:28808056 doi:http://dx.doi.org/10.1074/jbc.M117.791756
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